Teprenone (Eisai Co., Ltd.) is a mixture of (5E,9E,13E)-geranylgeranylacetone and (5Z,9E,13E)-geranylgeranylacetone at a weight ratio of 3:2. Teprenone is widely used as an oral therapeutic agent for gastric ulcer.
The use of teprenone in the ophthalmic field has been suggested. For example, Patent Literature 1 teaches the use of teprenone as an active ingredient of a prophylactic or therapeutic agent for dry eye, eye strain, or eye dryness. Patent Literature 2 discloses a clear eye drop consisting of teprenone, a phospholipid, a synthetic surfactant, and water.
Geranylgeranylacetone with an unknown cis-trans isomer ratio (Eisai Co., Ltd.) is also known to be useful as an active ingredient of a therapeutic agent for a retinal disease.
For example, Patent Literature 3 teaches a method for ameliorating an ocular disease such as diabetic retinopathy and glaucoma in a patient, the method comprising administering geranylgeranylacetone to the patient to increase the expression or activity of a heat shock protein in an ocular tissue, and recruiting a stem cell to the ocular tissue, thereby ameliorating the ocular disease.
Non Patent Literature 1 teaches that intraperitoneal administration of geranylgeranylacetone to a retinal detachment-induced animal induced the expression of heat shock protein 70 and subsequently reduced the apoptosis of visual cells significantly.
Non Patent Literature 2 teaches that intraperitoneal administration of geranylgeranylacetone to a glaucoma rat model induced the expression of heat shock protein 72 and subsequently reduced retinal ganglion cell death and thereby ameliorated optic nerve damage.
Non Patent Literature 3 teaches that oral administration of geranylgeranylacetone to a mouse with visual cell damage induced by light irradiation induced thioredoxin and heat shock protein 72 in the retinal pigment epithelium. The literature also teaches that the release of thioredoxin from the retinal pigment epithelium plays a crucial role in maintaining visual cells and that geranylgeranylacetone is useful for the protection of visual cells against light damage.
Non Patent Literature 4 teaches that oral administration of geranylgeranylacetone to a mouse with retinal injury induced by ischemia significantly increased the number of surviving retinal neurons and that geranylgeranylacetone is useful for the treatment of retinal degenerative diseases that involve ischemic injury.
Non Patent Literature 5 teaches that oral administration of geranylgeranylacetone to a multiple sclerosis mouse model improved the visual function, reduced the number of degenerating axons in the optic nerve, and prevented cell loss in the ganglion.
Teprenone marketed by Eisai Co., Ltd. is a mixture of (5E,9E,13E)-geranylgeranylacetone and (5Z,9E,13E)-geranylgeranylacetone at a weight ratio of 3:2 (WO 2004/047822, JP-9-169639 A, JP Pat. No. 4621326, JP-2006-89393 A, the Japanese pharmacopoeia, 16th edition, and the package insert of Selbex). Hence geranylgeranylacetone described in Patent Literature 3 and Non Patent Literature 1 to 5 is also a mixture of (5E,9E,13E)-geranylgeranylacetone and (5Z,9E,13E)-geranylgeranylacetone at a weight ratio of 3:2. Teprenone marketed by companies other than Eisai Co., Ltd. are also mixtures of (5E,9E,13E)-geranylgeranylacetone and (5Z,9E,13E)-geranylgeranylacetone at a weight ratio of 3:2 (for example, see MSDS (Cat. No. 202-15733; Wako Pure Chemical Industries, Ltd.).
However, teprenone, which is a mixture of (5E,9E,13E)-geranylgeranylacetone and (5Z,9E,13E)-geranylgeranylacetone at a weight ratio of 3:2, lacks a practically sufficient ameliorating effect for a retinal disease.